Michele G. Sullivan

SAN FRANCISCO — Pregnancy outcomes for women with diabetes who maintain excellent glucose control during their pregnancy are very good, and are similar to those seen in the general population, according to the results of a retrospective study.

The study, conducted by the high-risk obstetrics/endocrinology clinic at the Nebraska Medical Center, Omaha, found a low rate of diabetes-related obstetric complications among a group of 100 women who attended the clinic during their pregnancies. The clinic has used a team approach, incorporating intensive insulin and specific targets, since 1997. That approach “can result in excellent glucose control in at least half of patients, with overall maternal and fetal outcomes similar to” those in the general population, Dr. Kara Meinke Baehr said in a poster presented at the annual meeting of the Endocrine Society. The team includes perinatologists, endocrinologists, certified diabetes educators, registered dietitians, a social worker, and a translator.

Dr. Meinke Baehr of the Nebraska Medical Center and her colleagues reviewed the records of 100 women whose pregnancies were managed at the clinic from 1997 to 2006. Fetal outcomes were compared with the Nebraska 2004 Vital Statistics report.

The mean age at enrollment in the clinic was 29 years; the mean prepregnancy body mass index was 32 kg/m

More than a third of the women (36%) had type 1 diabetes; 26% had type 2 diabetes; 26% had gestational diabetes managed with insulin; and 12% had gestational diabetes managed by diet.

Women with types 1 and 2 diabetes significantly improved their blood glucose levels during the second and third trimesters of their pregnancies. At 8 weeks, only 25% had a hemoglobin A1c (HbA1c) value of less than 7%. That number rose to 80% by week 16 and to 90% by week 24; it then dropped back to 80% by week 32.

By the second half of pregnancy, about half of the cohort was meeting the goal of an HbA1c value of 6% or less, a significant improvement from the first trimester.

Maternal complications during pregnancy included retinopathy (6%), proteinuria (38%), and pre-eclampsia (17%). There were 104 hospitalizations, more than half of which were for glucose control. One woman was admitted 10 times.

Insulin regimens were used in 115 of the 127 pregnancies (90%). At the time of delivery, 43% were taking four injections per day; 2% were taking one insulin injection per day; 22% were taking two injections per day; and 3% were taking three injections per day. In all, 20% were using an insulin pump.

There were 127 pregnancies among these women over the study period, including 121 live births with two sets of twins. Most of the deliveries (71%) were by cesarean section; the rest were vaginal.

The mean gestational age was 37 weeks. Apgar scores were good, with a mean of 7.4 at 1 minute and 8.5 at 5 minutes. The mean birth weight was 3,479 grams; 28% of the infants were macrosomic. Overall, 35% of the infants required a stay in the neonatal intensive care unit (mean length of stay, 16 days).

SAN FRANCISCO — Pregnancy outcomes for women with diabetes who maintain excellent glucose control during their pregnancy are very good, and are similar to those seen in the general population, according to the results of a retrospective study.

The study, conducted by the high-risk obstetrics/endocrinology clinic at the Nebraska Medical Center, Omaha, found a low rate of diabetes-related obstetric complications among a group of 100 women who attended the clinic during their pregnancies. The clinic has used a team approach, incorporating intensive insulin and specific targets, since 1997. That approach “can result in excellent glucose control in at least half of patients, with overall maternal and fetal outcomes similar to” those in the general population, Dr. Kara Meinke Baehr said in a poster presented at the annual meeting of the Endocrine Society. The team includes perinatologists, endocrinologists, certified diabetes educators, registered dietitians, a social worker, and a translator.

Dr. Meinke Baehr of the Nebraska Medical Center and her colleagues reviewed the records of 100 women whose pregnancies were managed at the clinic from 1997 to 2006. Fetal outcomes were compared with the Nebraska 2004 Vital Statistics report.

The mean age at enrollment in the clinic was 29 years; the mean prepregnancy body mass index was 32 kg/m

More than a third of the women (36%) had type 1 diabetes; 26% had type 2 diabetes; 26% had gestational diabetes managed with insulin; and 12% had gestational diabetes managed by diet.

Women with types 1 and 2 diabetes significantly improved their blood glucose levels during the second and third trimesters of their pregnancies. At 8 weeks, only 25% had a hemoglobin A1c (HbA1c) value of less than 7%. That number rose to 80% by week 16 and to 90% by week 24; it then dropped back to 80% by week 32.

By the second half of pregnancy, about half of the cohort was meeting the goal of an HbA1c value of 6% or less, a significant improvement from the first trimester.

Maternal complications during pregnancy included retinopathy (6%), proteinuria (38%), and pre-eclampsia (17%). There were 104 hospitalizations, more than half of which were for glucose control. One woman was admitted 10 times.

Insulin regimens were used in 115 of the 127 pregnancies (90%). At the time of delivery, 43% were taking four injections per day; 2% were taking one insulin injection per day; 22% were taking two injections per day; and 3% were taking three injections per day. In all, 20% were using an insulin pump.

There were 127 pregnancies among these women over the study period, including 121 live births with two sets of twins. Most of the deliveries (71%) were by cesarean section; the rest were vaginal.

The mean gestational age was 37 weeks. Apgar scores were good, with a mean of 7.4 at 1 minute and 8.5 at 5 minutes. The mean birth weight was 3,479 grams; 28% of the infants were macrosomic. Overall, 35% of the infants required a stay in the neonatal intensive care unit (mean length of stay, 16 days).

SAN FRANCISCO — Pregnancy outcomes for women with diabetes who maintain excellent glucose control during their pregnancy are very good, and are similar to those seen in the general population, according to the results of a retrospective study.

The study, conducted by the high-risk obstetrics/endocrinology clinic at the Nebraska Medical Center, Omaha, found a low rate of diabetes-related obstetric complications among a group of 100 women who attended the clinic during their pregnancies. The clinic has used a team approach, incorporating intensive insulin and specific targets, since 1997. That approach “can result in excellent glucose control in at least half of patients, with overall maternal and fetal outcomes similar to” those in the general population, Dr. Kara Meinke Baehr said in a poster presented at the annual meeting of the Endocrine Society. The team includes perinatologists, endocrinologists, certified diabetes educators, registered dietitians, a social worker, and a translator.

Dr. Meinke Baehr of the Nebraska Medical Center and her colleagues reviewed the records of 100 women whose pregnancies were managed at the clinic from 1997 to 2006. Fetal outcomes were compared with the Nebraska 2004 Vital Statistics report.

The mean age at enrollment in the clinic was 29 years; the mean prepregnancy body mass index was 32 kg/m

More than a third of the women (36%) had type 1 diabetes; 26% had type 2 diabetes; 26% had gestational diabetes managed with insulin; and 12% had gestational diabetes managed by diet.

Women with types 1 and 2 diabetes significantly improved their blood glucose levels during the second and third trimesters of their pregnancies. At 8 weeks, only 25% had a hemoglobin A1c (HbA1c) value of less than 7%. That number rose to 80% by week 16 and to 90% by week 24; it then dropped back to 80% by week 32.

By the second half of pregnancy, about half of the cohort was meeting the goal of an HbA1c value of 6% or less, a significant improvement from the first trimester.

Maternal complications during pregnancy included retinopathy (6%), proteinuria (38%), and pre-eclampsia (17%). There were 104 hospitalizations, more than half of which were for glucose control. One woman was admitted 10 times.

Insulin regimens were used in 115 of the 127 pregnancies (90%). At the time of delivery, 43% were taking four injections per day; 2% were taking one insulin injection per day; 22% were taking two injections per day; and 3% were taking three injections per day. In all, 20% were using an insulin pump.

There were 127 pregnancies among these women over the study period, including 121 live births with two sets of twins. Most of the deliveries (71%) were by cesarean section; the rest were vaginal.

The mean gestational age was 37 weeks. Apgar scores were good, with a mean of 7.4 at 1 minute and 8.5 at 5 minutes. The mean birth weight was 3,479 grams; 28% of the infants were macrosomic. Overall, 35% of the infants required a stay in the neonatal intensive care unit (mean length of stay, 16 days).

SAN FRANCISCO — Even moderate physical fitness appears to confer a significant survival benefit on men with type 2 diabetes, no matter what their body weight, according to Roshney Jacob-Issac, Ph.D.

Her retrospective study, presented at the annual meeting of the Endocrine Society, found an inverse association between mortality and increasing fitness, with normal- and overweight men gaining even more survival benefits as they reached the highest fitness levels. Although obese men didn't reap any extra survival benefit with the top fitness level, moderate fitness decreased their overall risk of death by 52%.

“Increasing physical fitness has a survival benefit in diabetes regardless of body mass index,” said Dr. Jacob-Issac of the Veterans Affairs Medical Center, in Washington.

Her retrospective study examined the link between all-cause mortality and exercise capacity in 2,690 men with type 2 diabetes, all of whom were referred for exercise tolerance testing at VA centers in Washington or Palo Alto, Calif. Nearly half of the men (1,196) were obese; 1,088 were overweight, and 406 had a normal BMI.

Peak work load, which was determined via a stress test, was estimated in metabolic equivalents (METs). One MET equals the energy expenditure at rest, or an oxygen consumption of 3.5 mL/kg per minute. Based on peak workload, individuals were categorized as low fit (5 or fewer METs), moderately fit (5.1-8 METs), or highly fit (more than 8 METs). All-cause mortality was assessed at a mean of 7 years.

Overall there were 762 deaths (172 in the normal-weight group, 334 in the overweight group and 256 in the obese group). After adjustment for age, cardiac medications, and cardiovascular disease risk factors, Dr. Jacob-Issac found a strong, graded relationship between increasing fitness and decreasing mortality in all three groups.

In those men with a normal body weight, moderate fitness conferred a 40% reduction in the risk of death and high fitness conferred a 60% risk reduction, compared with low fitness. In overweight men, the risk reduction was 40% for moderate fitness and 65% for high fitness, compared with low fitness.

Among obese men, moderate fitness conferred a 52% reduction in the risk of death, but being highly fit conferred no additional protection.

Dr. Jacob-Issac reported no conflict of interest related to the study.

SAN FRANCISCO — Even moderate physical fitness appears to confer a significant survival benefit on men with type 2 diabetes, no matter what their body weight, according to Roshney Jacob-Issac, Ph.D.

Her retrospective study, presented at the annual meeting of the Endocrine Society, found an inverse association between mortality and increasing fitness, with normal- and overweight men gaining even more survival benefits as they reached the highest fitness levels. Although obese men didn't reap any extra survival benefit with the top fitness level, moderate fitness decreased their overall risk of death by 52%.

“Increasing physical fitness has a survival benefit in diabetes regardless of body mass index,” said Dr. Jacob-Issac of the Veterans Affairs Medical Center, in Washington.

Her retrospective study examined the link between all-cause mortality and exercise capacity in 2,690 men with type 2 diabetes, all of whom were referred for exercise tolerance testing at VA centers in Washington or Palo Alto, Calif. Nearly half of the men (1,196) were obese; 1,088 were overweight, and 406 had a normal BMI.

Peak work load, which was determined via a stress test, was estimated in metabolic equivalents (METs). One MET equals the energy expenditure at rest, or an oxygen consumption of 3.5 mL/kg per minute. Based on peak workload, individuals were categorized as low fit (5 or fewer METs), moderately fit (5.1-8 METs), or highly fit (more than 8 METs). All-cause mortality was assessed at a mean of 7 years.

Overall there were 762 deaths (172 in the normal-weight group, 334 in the overweight group and 256 in the obese group). After adjustment for age, cardiac medications, and cardiovascular disease risk factors, Dr. Jacob-Issac found a strong, graded relationship between increasing fitness and decreasing mortality in all three groups.

In those men with a normal body weight, moderate fitness conferred a 40% reduction in the risk of death and high fitness conferred a 60% risk reduction, compared with low fitness. In overweight men, the risk reduction was 40% for moderate fitness and 65% for high fitness, compared with low fitness.

Among obese men, moderate fitness conferred a 52% reduction in the risk of death, but being highly fit conferred no additional protection.

Dr. Jacob-Issac reported no conflict of interest related to the study.

SAN FRANCISCO — Even moderate physical fitness appears to confer a significant survival benefit on men with type 2 diabetes, no matter what their body weight, according to Roshney Jacob-Issac, Ph.D.

Her retrospective study, presented at the annual meeting of the Endocrine Society, found an inverse association between mortality and increasing fitness, with normal- and overweight men gaining even more survival benefits as they reached the highest fitness levels. Although obese men didn't reap any extra survival benefit with the top fitness level, moderate fitness decreased their overall risk of death by 52%.

“Increasing physical fitness has a survival benefit in diabetes regardless of body mass index,” said Dr. Jacob-Issac of the Veterans Affairs Medical Center, in Washington.

Her retrospective study examined the link between all-cause mortality and exercise capacity in 2,690 men with type 2 diabetes, all of whom were referred for exercise tolerance testing at VA centers in Washington or Palo Alto, Calif. Nearly half of the men (1,196) were obese; 1,088 were overweight, and 406 had a normal BMI.

Peak work load, which was determined via a stress test, was estimated in metabolic equivalents (METs). One MET equals the energy expenditure at rest, or an oxygen consumption of 3.5 mL/kg per minute. Based on peak workload, individuals were categorized as low fit (5 or fewer METs), moderately fit (5.1-8 METs), or highly fit (more than 8 METs). All-cause mortality was assessed at a mean of 7 years.

Overall there were 762 deaths (172 in the normal-weight group, 334 in the overweight group and 256 in the obese group). After adjustment for age, cardiac medications, and cardiovascular disease risk factors, Dr. Jacob-Issac found a strong, graded relationship between increasing fitness and decreasing mortality in all three groups.

In those men with a normal body weight, moderate fitness conferred a 40% reduction in the risk of death and high fitness conferred a 60% risk reduction, compared with low fitness. In overweight men, the risk reduction was 40% for moderate fitness and 65% for high fitness, compared with low fitness.

Among obese men, moderate fitness conferred a 52% reduction in the risk of death, but being highly fit conferred no additional protection.

Dr. Jacob-Issac reported no conflict of interest related to the study.

SAN FRANCISCO — Pregnancy outcomes for women with diabetes who maintain excellent glucose control during their pregnancy are very good, and are similar to those seen in the general population, according to the results of a retrospective study.

The study, conducted by the high-risk obstetrics/endocrinology clinic at the Nebraska Medical Center, Omaha, found a low rate of diabetes-related obstetric complications among a group of 100 women who attended the clinic during their pregnancies.

The clinic has used a team approach, incorporating intensive insulin and specific targets, since 1997. That approach “can result in excellent glucose control in at least half of patients, with overall maternal and fetal outcomes similar to” those in the general population, Dr. Kara Meinke Baehr said in a poster presented at the annual meeting of the Endocrine Society. The team includes perinatologists, endocrinologists, certified diabetes educators, registered dietitians, a social worker, and a translator.

Dr. Meinke Baehr of the Nebraska Medical Center and her colleagues reviewed the records of 100 women whose pregnancies were managed at the clinic from 1997 to 2006. Fetal outcomes were compared with the Nebraska 2004 Vital Statistics report.

The mean age at enrollment in the clinic was 29 years; the mean prepregnancy body mass index was 32 kg/m

More than a third of the women (36%) had type 1 diabetes; 26% had type 2 diabetes; 26% had gestational diabetes managed with insulin; and 12% had gestational diabetes managed by diet.

Women with types 1 and 2 diabetes significantly improved their blood glucose levels during the second and third trimesters of their pregnancies. At 8 weeks, only 25% had a hemoglobin A1c (HbA1c) value of less than 7%. That number rose to 80% by week 16 and to 90% by week 24; it then dropped back to 80% by week 32.

By the second half of pregnancy, about half of the cohort was meeting the goal of an HbA1c value of 6% or less, a significant improvement from the first trimester.

Maternal complications during pregnancy included retinopathy (6%), proteinuria (38%), and pre-eclampsia (17%). There were 104 hospitalizations, more than half of which were for glucose control. One woman was admitted 10 times.

Insulin regimens were used in 115 of the 127 pregnancies (90%). At the time of delivery, 43% were taking four injections per day; 2% were taking one insulin injection per day; 22% were taking two injections per day; and 3% were taking three injections per day. In all, 20% were using an insulin pump.

There were 127 pregnancies among these women over the study period, including 121 live births with two sets of twins. Most of the deliveries (71%) were by cesarean section; the rest were vaginal.

The mean gestational age was 37 weeks. Apgar scores were good, with a mean of 7.4 at 1 minute and 8.5 at 5 minutes. The mean birth weight was 3,479 grams; 28% of the infants were macrosomic. Overall, 35% of the infants required a stay in the neonatal intensive care unit (mean length of stay, 16 days).

The rate of birth trauma was 2%; traumas included Erb's palsy and shoulder dystocia. The rate of birth defects was 7%. Such defects included one schizencephaly, one tracheoesophageal fistula, one transposition of the great vessels, one polydactyly, and two cases of patent ductus arteriosus.

All rates were lower than those in the 2004 Nebraska state report, but comparisons can't be drawn because of the small study sample, Dr. Meinke Baehr noted.

SAN FRANCISCO — Pregnancy outcomes for women with diabetes who maintain excellent glucose control during their pregnancy are very good, and are similar to those seen in the general population, according to the results of a retrospective study.

The study, conducted by the high-risk obstetrics/endocrinology clinic at the Nebraska Medical Center, Omaha, found a low rate of diabetes-related obstetric complications among a group of 100 women who attended the clinic during their pregnancies.

The clinic has used a team approach, incorporating intensive insulin and specific targets, since 1997. That approach “can result in excellent glucose control in at least half of patients, with overall maternal and fetal outcomes similar to” those in the general population, Dr. Kara Meinke Baehr said in a poster presented at the annual meeting of the Endocrine Society. The team includes perinatologists, endocrinologists, certified diabetes educators, registered dietitians, a social worker, and a translator.

Dr. Meinke Baehr of the Nebraska Medical Center and her colleagues reviewed the records of 100 women whose pregnancies were managed at the clinic from 1997 to 2006. Fetal outcomes were compared with the Nebraska 2004 Vital Statistics report.

The mean age at enrollment in the clinic was 29 years; the mean prepregnancy body mass index was 32 kg/m

More than a third of the women (36%) had type 1 diabetes; 26% had type 2 diabetes; 26% had gestational diabetes managed with insulin; and 12% had gestational diabetes managed by diet.

Women with types 1 and 2 diabetes significantly improved their blood glucose levels during the second and third trimesters of their pregnancies. At 8 weeks, only 25% had a hemoglobin A1c (HbA1c) value of less than 7%. That number rose to 80% by week 16 and to 90% by week 24; it then dropped back to 80% by week 32.

By the second half of pregnancy, about half of the cohort was meeting the goal of an HbA1c value of 6% or less, a significant improvement from the first trimester.

Maternal complications during pregnancy included retinopathy (6%), proteinuria (38%), and pre-eclampsia (17%). There were 104 hospitalizations, more than half of which were for glucose control. One woman was admitted 10 times.

Insulin regimens were used in 115 of the 127 pregnancies (90%). At the time of delivery, 43% were taking four injections per day; 2% were taking one insulin injection per day; 22% were taking two injections per day; and 3% were taking three injections per day. In all, 20% were using an insulin pump.

There were 127 pregnancies among these women over the study period, including 121 live births with two sets of twins. Most of the deliveries (71%) were by cesarean section; the rest were vaginal.

The mean gestational age was 37 weeks. Apgar scores were good, with a mean of 7.4 at 1 minute and 8.5 at 5 minutes. The mean birth weight was 3,479 grams; 28% of the infants were macrosomic. Overall, 35% of the infants required a stay in the neonatal intensive care unit (mean length of stay, 16 days).

The rate of birth trauma was 2%; traumas included Erb's palsy and shoulder dystocia. The rate of birth defects was 7%. Such defects included one schizencephaly, one tracheoesophageal fistula, one transposition of the great vessels, one polydactyly, and two cases of patent ductus arteriosus.

All rates were lower than those in the 2004 Nebraska state report, but comparisons can't be drawn because of the small study sample, Dr. Meinke Baehr noted.

SAN FRANCISCO — Pregnancy outcomes for women with diabetes who maintain excellent glucose control during their pregnancy are very good, and are similar to those seen in the general population, according to the results of a retrospective study.

The study, conducted by the high-risk obstetrics/endocrinology clinic at the Nebraska Medical Center, Omaha, found a low rate of diabetes-related obstetric complications among a group of 100 women who attended the clinic during their pregnancies.

The clinic has used a team approach, incorporating intensive insulin and specific targets, since 1997. That approach “can result in excellent glucose control in at least half of patients, with overall maternal and fetal outcomes similar to” those in the general population, Dr. Kara Meinke Baehr said in a poster presented at the annual meeting of the Endocrine Society. The team includes perinatologists, endocrinologists, certified diabetes educators, registered dietitians, a social worker, and a translator.

Dr. Meinke Baehr of the Nebraska Medical Center and her colleagues reviewed the records of 100 women whose pregnancies were managed at the clinic from 1997 to 2006. Fetal outcomes were compared with the Nebraska 2004 Vital Statistics report.

The mean age at enrollment in the clinic was 29 years; the mean prepregnancy body mass index was 32 kg/m

More than a third of the women (36%) had type 1 diabetes; 26% had type 2 diabetes; 26% had gestational diabetes managed with insulin; and 12% had gestational diabetes managed by diet.

Women with types 1 and 2 diabetes significantly improved their blood glucose levels during the second and third trimesters of their pregnancies. At 8 weeks, only 25% had a hemoglobin A1c (HbA1c) value of less than 7%. That number rose to 80% by week 16 and to 90% by week 24; it then dropped back to 80% by week 32.

By the second half of pregnancy, about half of the cohort was meeting the goal of an HbA1c value of 6% or less, a significant improvement from the first trimester.

Maternal complications during pregnancy included retinopathy (6%), proteinuria (38%), and pre-eclampsia (17%). There were 104 hospitalizations, more than half of which were for glucose control. One woman was admitted 10 times.

Insulin regimens were used in 115 of the 127 pregnancies (90%). At the time of delivery, 43% were taking four injections per day; 2% were taking one insulin injection per day; 22% were taking two injections per day; and 3% were taking three injections per day. In all, 20% were using an insulin pump.

There were 127 pregnancies among these women over the study period, including 121 live births with two sets of twins. Most of the deliveries (71%) were by cesarean section; the rest were vaginal.

The mean gestational age was 37 weeks. Apgar scores were good, with a mean of 7.4 at 1 minute and 8.5 at 5 minutes. The mean birth weight was 3,479 grams; 28% of the infants were macrosomic. Overall, 35% of the infants required a stay in the neonatal intensive care unit (mean length of stay, 16 days).

The rate of birth trauma was 2%; traumas included Erb's palsy and shoulder dystocia. The rate of birth defects was 7%. Such defects included one schizencephaly, one tracheoesophageal fistula, one transposition of the great vessels, one polydactyly, and two cases of patent ductus arteriosus.

All rates were lower than those in the 2004 Nebraska state report, but comparisons can't be drawn because of the small study sample, Dr. Meinke Baehr noted.

CHICAGO — An experimental drug that attacks neurofibrillary tau tangles significantly improved some measures of memory in mild cognitive impairment, but failed to meet its primary cognitive end point.

Because of its effects on visual and verbal memory, AL-108 will move on to phase II, Dr. Donald E. Schmechel said at the International Conference on Alzheimer's Disease.

“Twelve weeks of AL-108 resulted in statistically significant, dose-dependent, and durable improvement on measures of short-term memory, including visual, verbal, and auditory working memory, which is a type of memory function that deteriorates throughout the progression of Alzheimer's,” said Dr. Schmechel. “This makes AL-108 the first drug to validate in humans the importance of the tangle, or tau, pathway in the disease.”

Neurofibrillary tau tangles, a diagnostic hallmark of Alzheimer's, are composed of hyperphosphorylated tau, a protein that normally occurs in neurons. In its hyperphosphorylated state, tau forms tangled fibrils that interfere with neuronal function. AL-108, developed by Allon Therapeutics Inc. of Vancouver, is the first drug in development to exert action on those tangles.

Many more Alzheimer's drugs under investigation target the amyloid pathway of neurodegeneration. Dr. Schmechel, whose research was funded by Allon, said AL-108's success shows that tangles also can be a target. “'Tangles' may be as important—or perhaps more important—than 'plaques.'”

The phase IIa study comprised 144 patients (mean age 69) with amnestic mild cognitive impairment. Patients had a Mini-Mental State Examination of at least 24. They were divided into three groups: placebo, 5 mg AL-108 daily, and 15 mg AL-108 twice daily. The drug was administered for 12 weeks; cognition was tested at baseline and at weeks 4, 8, 12, and 16.

The drug was safe and well tolerated, Dr. Schmechel said at the meeting presented by the Alzheimer's Association. The dropout rate was 13% and not different between the active and placebo groups. Compliance was high (98%). The most common adverse event was headache, but there was no difference in incidence between the active and placebo groups.

The primary end point was a composite of memory component scores from four cognitive tests. By 16 weeks, neither of the active groups scored significantly better than the placebo group on this measure. However, those taking the higher dose showed a trend toward better performance, noted Dr. Schmechel, professor of neurology at Duke University, Durham, N.C.

On the digit span forward test—a measure of verbal recall and short-term memory—the high-dose group performed significantly better than the low-dose or placebo groups, with a 12% increase over baseline. The high-dose group also performed significantly better than the others on the delayed match-to-sample test, a measure of visual working memory. By week 16, these patients had a 62% improvement over baseline.

CHICAGO — An experimental drug that attacks neurofibrillary tau tangles significantly improved some measures of memory in mild cognitive impairment, but failed to meet its primary cognitive end point.

Because of its effects on visual and verbal memory, AL-108 will move on to phase II, Dr. Donald E. Schmechel said at the International Conference on Alzheimer's Disease.

“Twelve weeks of AL-108 resulted in statistically significant, dose-dependent, and durable improvement on measures of short-term memory, including visual, verbal, and auditory working memory, which is a type of memory function that deteriorates throughout the progression of Alzheimer's,” said Dr. Schmechel. “This makes AL-108 the first drug to validate in humans the importance of the tangle, or tau, pathway in the disease.”

Neurofibrillary tau tangles, a diagnostic hallmark of Alzheimer's, are composed of hyperphosphorylated tau, a protein that normally occurs in neurons. In its hyperphosphorylated state, tau forms tangled fibrils that interfere with neuronal function. AL-108, developed by Allon Therapeutics Inc. of Vancouver, is the first drug in development to exert action on those tangles.

Many more Alzheimer's drugs under investigation target the amyloid pathway of neurodegeneration. Dr. Schmechel, whose research was funded by Allon, said AL-108's success shows that tangles also can be a target. “'Tangles' may be as important—or perhaps more important—than 'plaques.'”

The phase IIa study comprised 144 patients (mean age 69) with amnestic mild cognitive impairment. Patients had a Mini-Mental State Examination of at least 24. They were divided into three groups: placebo, 5 mg AL-108 daily, and 15 mg AL-108 twice daily. The drug was administered for 12 weeks; cognition was tested at baseline and at weeks 4, 8, 12, and 16.

The drug was safe and well tolerated, Dr. Schmechel said at the meeting presented by the Alzheimer's Association. The dropout rate was 13% and not different between the active and placebo groups. Compliance was high (98%). The most common adverse event was headache, but there was no difference in incidence between the active and placebo groups.

The primary end point was a composite of memory component scores from four cognitive tests. By 16 weeks, neither of the active groups scored significantly better than the placebo group on this measure. However, those taking the higher dose showed a trend toward better performance, noted Dr. Schmechel, professor of neurology at Duke University, Durham, N.C.

On the digit span forward test—a measure of verbal recall and short-term memory—the high-dose group performed significantly better than the low-dose or placebo groups, with a 12% increase over baseline. The high-dose group also performed significantly better than the others on the delayed match-to-sample test, a measure of visual working memory. By week 16, these patients had a 62% improvement over baseline.

CHICAGO — An experimental drug that attacks neurofibrillary tau tangles significantly improved some measures of memory in mild cognitive impairment, but failed to meet its primary cognitive end point.

Because of its effects on visual and verbal memory, AL-108 will move on to phase II, Dr. Donald E. Schmechel said at the International Conference on Alzheimer's Disease.

“Twelve weeks of AL-108 resulted in statistically significant, dose-dependent, and durable improvement on measures of short-term memory, including visual, verbal, and auditory working memory, which is a type of memory function that deteriorates throughout the progression of Alzheimer's,” said Dr. Schmechel. “This makes AL-108 the first drug to validate in humans the importance of the tangle, or tau, pathway in the disease.”

Neurofibrillary tau tangles, a diagnostic hallmark of Alzheimer's, are composed of hyperphosphorylated tau, a protein that normally occurs in neurons. In its hyperphosphorylated state, tau forms tangled fibrils that interfere with neuronal function. AL-108, developed by Allon Therapeutics Inc. of Vancouver, is the first drug in development to exert action on those tangles.

Many more Alzheimer's drugs under investigation target the amyloid pathway of neurodegeneration. Dr. Schmechel, whose research was funded by Allon, said AL-108's success shows that tangles also can be a target. “'Tangles' may be as important—or perhaps more important—than 'plaques.'”

The phase IIa study comprised 144 patients (mean age 69) with amnestic mild cognitive impairment. Patients had a Mini-Mental State Examination of at least 24. They were divided into three groups: placebo, 5 mg AL-108 daily, and 15 mg AL-108 twice daily. The drug was administered for 12 weeks; cognition was tested at baseline and at weeks 4, 8, 12, and 16.

The drug was safe and well tolerated, Dr. Schmechel said at the meeting presented by the Alzheimer's Association. The dropout rate was 13% and not different between the active and placebo groups. Compliance was high (98%). The most common adverse event was headache, but there was no difference in incidence between the active and placebo groups.

The primary end point was a composite of memory component scores from four cognitive tests. By 16 weeks, neither of the active groups scored significantly better than the placebo group on this measure. However, those taking the higher dose showed a trend toward better performance, noted Dr. Schmechel, professor of neurology at Duke University, Durham, N.C.

On the digit span forward test—a measure of verbal recall and short-term memory—the high-dose group performed significantly better than the low-dose or placebo groups, with a 12% increase over baseline. The high-dose group also performed significantly better than the others on the delayed match-to-sample test, a measure of visual working memory. By week 16, these patients had a 62% improvement over baseline.

CHICAGO — Tarenflurbil, a drug designed to reduce toxic amyloid β levels in the brains of Alzheimer's disease patients, has failed its large phase III trial, Dr. Robert Green reported at the International Conference on Alzheimer's Disease.

Patients who received the drug (800 mg twice daily) exhibited virtually the same declines in cognition and function as did those who received placebo, said Dr. Green of the Boston University. “I think the results are definitive. There was no efficacy of the compound in this trial.”

In the wake of these results, Myriad Genetics Inc. of Salt Lake City, has decided to scrap its research on the drug, Dr. Green said at the meeting presented by the Alzheimer's Association.

Tarenflurbil had a somewhat encouraging phase II trial. In that study of 207 patients, those taking tarenflurbil experienced significant improvements in global functioning and activities of daily living, and near-significant improvements in cognition.

No such benefits occurred in the phase III trial, which comprised 1,653 patients with mild Alzheimer's. It was conducted at 133 sites across the United States.

Patients were randomized to equal groups to the study drug or placebo for 18 months; the treatment period was followed by a 30-day washout. Primary end points were the Alzheimer's Disease Assessment Scale-cognition (ADAS-Cog) and the Alzheimer's Disease Assessment Scale-activities of daily living (ADAS-ADL). Patients were evaluated every 3 months.

The groups were well matched at baseline, with an average age of 74 years and an average Mini-Mental State Exam score of 23; 51% were female. Most of the patients were on concomitant antidementia drugs: 33% were taking only cholinesterase inhibitors, 6% were on memantine alone, 19% were taking no antidementia drugs, and the rest were on combination therapy.

After 18 months of treatment, both the active and placebo groups showed a steady and almost identical decline in cognition. Both groups lost 7 points on the ADAS-cog scale by the end of the study. In a secondary cognitive measure, the Clinical Dementia Rating sum of boxes, both groups lost 2.5 points by the end of the study.

A similar pattern appeared on the ADAS-ADL scale. Both groups followed an almost identical pattern of decline, each losing 10 points on the scale by 18 months.

Overall adverse events were similar in the tarenflurbil and placebo arms (88% vs. 86%). More patients taking the study drug discontinued because of adverse events (18% vs. 12%). Serious adverse events occurred in 23% of the active group and 20% of the placebo group.

The most common adverse event was anemia (10% tarenflurbil vs. 4% placebo—a significant difference). Infection was also significantly more common among the active group (7% vs. 3%), as was gastrointestinal ulcer (2% vs. 0.4%). There was no difference in the incidence of gastrointestinal bleeding.

Although the trial was a failure in terms of tarenflurbil efficacy, it did confirm an important observation—one that will be greatly helpful in future AD drug trials, Dr. Green said. “This study, which was well designed and well powered, proved that patients with mild Alzheimer's disease do decline enough over 18 months to actually look for a signal of efficacy.”

Tarenflurbil was the first gamma secretase modulator to be tested in a phase III trial. This class of drug is thought to reduce the levels of toxic amyloid β (Aβ₄₂) in the brain by changing the point at which the enzyme gamma secretase cuts the amyloid precursor protein.

“This shifts the ratio to less of the toxic Aβ₄₂ and more of the less-toxic Aβ₄₀,” Dr. Green said.

Dr. Green said he did not receive compensation from Myriad Genetics for being a primary investigator on the study.

'I think the results are definitive. There was no efficacy of the compound in this trial.' DR. GREEN

CHICAGO — Tarenflurbil, a drug designed to reduce toxic amyloid β levels in the brains of Alzheimer's disease patients, has failed its large phase III trial, Dr. Robert Green reported at the International Conference on Alzheimer's Disease.

Patients who received the drug (800 mg twice daily) exhibited virtually the same declines in cognition and function as did those who received placebo, said Dr. Green of the Boston University. “I think the results are definitive. There was no efficacy of the compound in this trial.”

In the wake of these results, Myriad Genetics Inc. of Salt Lake City, has decided to scrap its research on the drug, Dr. Green said at the meeting presented by the Alzheimer's Association.

Tarenflurbil had a somewhat encouraging phase II trial. In that study of 207 patients, those taking tarenflurbil experienced significant improvements in global functioning and activities of daily living, and near-significant improvements in cognition.

No such benefits occurred in the phase III trial, which comprised 1,653 patients with mild Alzheimer's. It was conducted at 133 sites across the United States.

Patients were randomized to equal groups to the study drug or placebo for 18 months; the treatment period was followed by a 30-day washout. Primary end points were the Alzheimer's Disease Assessment Scale-cognition (ADAS-Cog) and the Alzheimer's Disease Assessment Scale-activities of daily living (ADAS-ADL). Patients were evaluated every 3 months.

The groups were well matched at baseline, with an average age of 74 years and an average Mini-Mental State Exam score of 23; 51% were female. Most of the patients were on concomitant antidementia drugs: 33% were taking only cholinesterase inhibitors, 6% were on memantine alone, 19% were taking no antidementia drugs, and the rest were on combination therapy.

After 18 months of treatment, both the active and placebo groups showed a steady and almost identical decline in cognition. Both groups lost 7 points on the ADAS-cog scale by the end of the study. In a secondary cognitive measure, the Clinical Dementia Rating sum of boxes, both groups lost 2.5 points by the end of the study.

A similar pattern appeared on the ADAS-ADL scale. Both groups followed an almost identical pattern of decline, each losing 10 points on the scale by 18 months.

Overall adverse events were similar in the tarenflurbil and placebo arms (88% vs. 86%). More patients taking the study drug discontinued because of adverse events (18% vs. 12%). Serious adverse events occurred in 23% of the active group and 20% of the placebo group.

The most common adverse event was anemia (10% tarenflurbil vs. 4% placebo—a significant difference). Infection was also significantly more common among the active group (7% vs. 3%), as was gastrointestinal ulcer (2% vs. 0.4%). There was no difference in the incidence of gastrointestinal bleeding.

Although the trial was a failure in terms of tarenflurbil efficacy, it did confirm an important observation—one that will be greatly helpful in future AD drug trials, Dr. Green said. “This study, which was well designed and well powered, proved that patients with mild Alzheimer's disease do decline enough over 18 months to actually look for a signal of efficacy.”

Tarenflurbil was the first gamma secretase modulator to be tested in a phase III trial. This class of drug is thought to reduce the levels of toxic amyloid β (Aβ₄₂) in the brain by changing the point at which the enzyme gamma secretase cuts the amyloid precursor protein.

“This shifts the ratio to less of the toxic Aβ₄₂ and more of the less-toxic Aβ₄₀,” Dr. Green said.

Dr. Green said he did not receive compensation from Myriad Genetics for being a primary investigator on the study.

'I think the results are definitive. There was no efficacy of the compound in this trial.' DR. GREEN

CHICAGO — Tarenflurbil, a drug designed to reduce toxic amyloid β levels in the brains of Alzheimer's disease patients, has failed its large phase III trial, Dr. Robert Green reported at the International Conference on Alzheimer's Disease.

Patients who received the drug (800 mg twice daily) exhibited virtually the same declines in cognition and function as did those who received placebo, said Dr. Green of the Boston University. “I think the results are definitive. There was no efficacy of the compound in this trial.”

In the wake of these results, Myriad Genetics Inc. of Salt Lake City, has decided to scrap its research on the drug, Dr. Green said at the meeting presented by the Alzheimer's Association.

Tarenflurbil had a somewhat encouraging phase II trial. In that study of 207 patients, those taking tarenflurbil experienced significant improvements in global functioning and activities of daily living, and near-significant improvements in cognition.

No such benefits occurred in the phase III trial, which comprised 1,653 patients with mild Alzheimer's. It was conducted at 133 sites across the United States.

Patients were randomized to equal groups to the study drug or placebo for 18 months; the treatment period was followed by a 30-day washout. Primary end points were the Alzheimer's Disease Assessment Scale-cognition (ADAS-Cog) and the Alzheimer's Disease Assessment Scale-activities of daily living (ADAS-ADL). Patients were evaluated every 3 months.

The groups were well matched at baseline, with an average age of 74 years and an average Mini-Mental State Exam score of 23; 51% were female. Most of the patients were on concomitant antidementia drugs: 33% were taking only cholinesterase inhibitors, 6% were on memantine alone, 19% were taking no antidementia drugs, and the rest were on combination therapy.

After 18 months of treatment, both the active and placebo groups showed a steady and almost identical decline in cognition. Both groups lost 7 points on the ADAS-cog scale by the end of the study. In a secondary cognitive measure, the Clinical Dementia Rating sum of boxes, both groups lost 2.5 points by the end of the study.

A similar pattern appeared on the ADAS-ADL scale. Both groups followed an almost identical pattern of decline, each losing 10 points on the scale by 18 months.

Overall adverse events were similar in the tarenflurbil and placebo arms (88% vs. 86%). More patients taking the study drug discontinued because of adverse events (18% vs. 12%). Serious adverse events occurred in 23% of the active group and 20% of the placebo group.

The most common adverse event was anemia (10% tarenflurbil vs. 4% placebo—a significant difference). Infection was also significantly more common among the active group (7% vs. 3%), as was gastrointestinal ulcer (2% vs. 0.4%). There was no difference in the incidence of gastrointestinal bleeding.

Although the trial was a failure in terms of tarenflurbil efficacy, it did confirm an important observation—one that will be greatly helpful in future AD drug trials, Dr. Green said. “This study, which was well designed and well powered, proved that patients with mild Alzheimer's disease do decline enough over 18 months to actually look for a signal of efficacy.”

Tarenflurbil was the first gamma secretase modulator to be tested in a phase III trial. This class of drug is thought to reduce the levels of toxic amyloid β (Aβ₄₂) in the brain by changing the point at which the enzyme gamma secretase cuts the amyloid precursor protein.

“This shifts the ratio to less of the toxic Aβ₄₂ and more of the less-toxic Aβ₄₀,” Dr. Green said.

Dr. Green said he did not receive compensation from Myriad Genetics for being a primary investigator on the study.

'I think the results are definitive. There was no efficacy of the compound in this trial.' DR. GREEN

SAN FRANCISCO — Metformin is associated with modest weight loss and some improvements in signs of metabolic syndrome in obese children with severe hyperinsulinemia, a government-sponsored randomized controlled trial has concluded.

But because this is the first such study in children, the drug can't yet be recommended for routine use in this population, Dr. Jack Yanovski said at the annual meeting of the Endocrine Society.

Dr. Yanovski, chief of the National Institutes of Child Health and Human Development's Unit on Growth and Obesity, presented the results of the first placebo-controlled trial of metformin in children aged 6–12 years. The 100 children who participated (mean age 10 years) were all obese (mean body mass index [BMI] 34.6 kg/m

The cohort consisted mostly of female children (60%). Children randomized to metformin (53) were started at 1,000 mg/day; this was ramped up to a final dosage of 1,000 mg twice a day for the duration of the 6-month trial. All children but one were able to tolerate the dose. All children also took a daily multivitamin supplement.

By the study's end, mean BMI had decreased in the active group and increased in the placebo group (−1 kg/m

Some signs of metabolic syndrome improved in children taking metformin, although the changes were not significant. Serum glucose, homeostatic assessment model algorithm (HOMA) insulin resistance index, and total cholesterol all improved in the treated children.

Children in the metformin group experienced a significant decrease in serum vitamin B12 concentrations, although all remained within normal range, and no child required additional supplementation.

The most commonly reported adverse events were liquid stool (60% metformin vs. 2.5% placebo), nausea (24% vs. 8%), and fatigue (14% vs. 5%). All were significantly more common in the metformin group; however, by the study's end, the incidence of liquid stool had decreased by 20% and the incidence of nausea had decreased by 8%.

Metformin also appears to exert its weight-loss effects in obese children by reducing their desire to eat and thus decreasing their food intake, according to a substudy of the same government-sponsored trial, Rachael Sorg said in a poster session at the Endocrine Society meeting.

Some of the children (45 metformin-treated and 39 placebo-treated) participated in both a pre- and posttreatment meal study to evaluate the drug's effect on food intake. One study was conducted before the drug trial commenced, and one at the end of the 6-month treatment period.

Each meal study included two buffet lunches, each containing 28 items (9,835 calories total). The first lunch was consumed after children fasted through the night. The second was consumed after they drank a 790-calorie nutrient shake for breakfast.

Subjects completed a scale of hunger, fullness, and desire to eat before after each test meal, and also kept a food diary of everything they consumed for 7 days before and after the test.

Compared with baseline measurements obtained in the pre-metformin meal study, children taking metformin consumed significantly fewer calories in the meal after the breakfast shake. They also reported significantly decreased feelings of hunger and increased feelings of fullness after the shake. They reported lower hunger after the postshake meal, lower desire to eat the postshake meal, and lower caloric intake at the postfast meal as well, although none of these differences were significant.

“These data suggest that one of the mechanisms whereby metformin treatment reduces body weight in overweight, hyperinsulinemic children is by decreasing food intake and perceived hunger,” said Ms. Sorg, a research assistant at the National Institutes of Child Health and Human Development.

Dr. Yanovski and Ms. Sorg said they had no financial disclosures to make with regard to metformin.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Metformin is associated with modest weight loss and some improvements in signs of metabolic syndrome in obese children with severe hyperinsulinemia, a government-sponsored randomized controlled trial has concluded.

But because this is the first such study in children, the drug can't yet be recommended for routine use in this population, Dr. Jack Yanovski said at the annual meeting of the Endocrine Society.

Dr. Yanovski, chief of the National Institutes of Child Health and Human Development's Unit on Growth and Obesity, presented the results of the first placebo-controlled trial of metformin in children aged 6–12 years. The 100 children who participated (mean age 10 years) were all obese (mean body mass index [BMI] 34.6 kg/m

The cohort consisted mostly of female children (60%). Children randomized to metformin (53) were started at 1,000 mg/day; this was ramped up to a final dosage of 1,000 mg twice a day for the duration of the 6-month trial. All children but one were able to tolerate the dose. All children also took a daily multivitamin supplement.

By the study's end, mean BMI had decreased in the active group and increased in the placebo group (−1 kg/m

Some signs of metabolic syndrome improved in children taking metformin, although the changes were not significant. Serum glucose, homeostatic assessment model algorithm (HOMA) insulin resistance index, and total cholesterol all improved in the treated children.

Children in the metformin group experienced a significant decrease in serum vitamin B12 concentrations, although all remained within normal range, and no child required additional supplementation.

The most commonly reported adverse events were liquid stool (60% metformin vs. 2.5% placebo), nausea (24% vs. 8%), and fatigue (14% vs. 5%). All were significantly more common in the metformin group; however, by the study's end, the incidence of liquid stool had decreased by 20% and the incidence of nausea had decreased by 8%.

Metformin also appears to exert its weight-loss effects in obese children by reducing their desire to eat and thus decreasing their food intake, according to a substudy of the same government-sponsored trial, Rachael Sorg said in a poster session at the Endocrine Society meeting.

Some of the children (45 metformin-treated and 39 placebo-treated) participated in both a pre- and posttreatment meal study to evaluate the drug's effect on food intake. One study was conducted before the drug trial commenced, and one at the end of the 6-month treatment period.

Each meal study included two buffet lunches, each containing 28 items (9,835 calories total). The first lunch was consumed after children fasted through the night. The second was consumed after they drank a 790-calorie nutrient shake for breakfast.

Subjects completed a scale of hunger, fullness, and desire to eat before after each test meal, and also kept a food diary of everything they consumed for 7 days before and after the test.

Compared with baseline measurements obtained in the pre-metformin meal study, children taking metformin consumed significantly fewer calories in the meal after the breakfast shake. They also reported significantly decreased feelings of hunger and increased feelings of fullness after the shake. They reported lower hunger after the postshake meal, lower desire to eat the postshake meal, and lower caloric intake at the postfast meal as well, although none of these differences were significant.

“These data suggest that one of the mechanisms whereby metformin treatment reduces body weight in overweight, hyperinsulinemic children is by decreasing food intake and perceived hunger,” said Ms. Sorg, a research assistant at the National Institutes of Child Health and Human Development.

Dr. Yanovski and Ms. Sorg said they had no financial disclosures to make with regard to metformin.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Metformin is associated with modest weight loss and some improvements in signs of metabolic syndrome in obese children with severe hyperinsulinemia, a government-sponsored randomized controlled trial has concluded.

But because this is the first such study in children, the drug can't yet be recommended for routine use in this population, Dr. Jack Yanovski said at the annual meeting of the Endocrine Society.

Dr. Yanovski, chief of the National Institutes of Child Health and Human Development's Unit on Growth and Obesity, presented the results of the first placebo-controlled trial of metformin in children aged 6–12 years. The 100 children who participated (mean age 10 years) were all obese (mean body mass index [BMI] 34.6 kg/m

The cohort consisted mostly of female children (60%). Children randomized to metformin (53) were started at 1,000 mg/day; this was ramped up to a final dosage of 1,000 mg twice a day for the duration of the 6-month trial. All children but one were able to tolerate the dose. All children also took a daily multivitamin supplement.

By the study's end, mean BMI had decreased in the active group and increased in the placebo group (−1 kg/m

Some signs of metabolic syndrome improved in children taking metformin, although the changes were not significant. Serum glucose, homeostatic assessment model algorithm (HOMA) insulin resistance index, and total cholesterol all improved in the treated children.

Children in the metformin group experienced a significant decrease in serum vitamin B12 concentrations, although all remained within normal range, and no child required additional supplementation.

The most commonly reported adverse events were liquid stool (60% metformin vs. 2.5% placebo), nausea (24% vs. 8%), and fatigue (14% vs. 5%). All were significantly more common in the metformin group; however, by the study's end, the incidence of liquid stool had decreased by 20% and the incidence of nausea had decreased by 8%.

Metformin also appears to exert its weight-loss effects in obese children by reducing their desire to eat and thus decreasing their food intake, according to a substudy of the same government-sponsored trial, Rachael Sorg said in a poster session at the Endocrine Society meeting.

Some of the children (45 metformin-treated and 39 placebo-treated) participated in both a pre- and posttreatment meal study to evaluate the drug's effect on food intake. One study was conducted before the drug trial commenced, and one at the end of the 6-month treatment period.

Each meal study included two buffet lunches, each containing 28 items (9,835 calories total). The first lunch was consumed after children fasted through the night. The second was consumed after they drank a 790-calorie nutrient shake for breakfast.

Subjects completed a scale of hunger, fullness, and desire to eat before after each test meal, and also kept a food diary of everything they consumed for 7 days before and after the test.

Compared with baseline measurements obtained in the pre-metformin meal study, children taking metformin consumed significantly fewer calories in the meal after the breakfast shake. They also reported significantly decreased feelings of hunger and increased feelings of fullness after the shake. They reported lower hunger after the postshake meal, lower desire to eat the postshake meal, and lower caloric intake at the postfast meal as well, although none of these differences were significant.

“These data suggest that one of the mechanisms whereby metformin treatment reduces body weight in overweight, hyperinsulinemic children is by decreasing food intake and perceived hunger,” said Ms. Sorg, a research assistant at the National Institutes of Child Health and Human Development.

Dr. Yanovski and Ms. Sorg said they had no financial disclosures to make with regard to metformin.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Pregnancy outcomes for women with diabetes who maintain excellent glucose control during their pregnancy are very good, and are similar to those seen in the general population, according to the results of a retrospective study.

The study, conducted by the high-risk obstetrics/endocrinology clinic at the Nebraska Medical Center, Omaha, found a low rate of diabetes-related obstetric complications in a group of 100 women who attended the clinic during their pregnancies.

The clinic has used a team approach, incorporating intensive insulin and specific targets, since 1997. That approach “can result in excellent glucose control in at least half of patients, with overall maternal and fetal outcomes similar to” those in the general population, Dr. Kara Meinke Baehr said in a poster presented at the annual meeting of the Endocrine Society.

The team includes perinatologists, endocrinologists, certified diabetes educators, registered dietitians, a social worker, and a translator.

Dr. Meinke Baehr of the Nebraska Medical Center and her colleagues reviewed the records of 100 women whose pregnancies were managed at the clinic from 1997 to 2006. Fetal outcomes were compared with the Nebraska 2004 Vital Statistics report.

The mean age at enrollment in the clinic was 29 years; the mean prepregnancy body mass index was 32 kg/m

More than a third of the women (36%) had type 1 diabetes; 26% had type 2 diabetes; 26% had gestational diabetes that was managed with insulin; and 12% had gestational diabetes that was managed by diet.

Women with types 1 and 2 diabetes significantly improved their blood glucose levels during the second and third trimesters of their pregnancies. At 8 weeks, only 25% had a hemoglobin A1c (HbA1c) value of less than 7%. That number rose to 80% by week 16 and to 90% by week 24; it then dropped back to 80% by week 32.

By the second half of pregnancy, about half of the cohort was meeting the goal of an HbA1c value of 6% or less, a significant improvement from the first trimester .

Maternal complications during pregnancy included retinopathy (6%), proteinuria (38%), and pre-eclampsia (17%). There were 104 hospitalizations, more than half of which were for glucose control. One of the women was admitted 10 times.

Insulin regimens were used in 115 of the 127 pregnancies (90%). At the time of delivery, 43% were taking four injections per day; 2% were taking one insulin injection per day; 22% were taking two injections per day; and 3% were taking three injections per day. In all, 20% of the women were using an insulin pump.

There were 127 pregnancies among these women over the study period, including 121 live births with two sets of twins. Most of the deliveries (71%) were by cesarean section; the rest were vaginal.

The mean gestational age was 37 weeks. Apgar scores were good, with a mean of 7.4 at 1 minute and 8.5 at 5 minutes. The mean birth weight was 3,479 grams; 28% of the infants were macrosomic. Overall, 35% of the infants required a stay in the neonatal intensive care unit (mean length of stay, 16 days).

The rate of birth trauma was 2%; traumas included Erb's palsy and shoulder dystocia. The rate of birth defects was 7%. Such defects included one schizencephaly, one tracheoesophageal fistula, one transposition of the great vessels, one polydactyly, and two cases of patent ductus arteriosus.

All of the rates were lower than those in the 2004 Nebraska state report, but comparisons can't be drawn because of the small study sample, Dr. Meinke Baehr noted.

SAN FRANCISCO — Pregnancy outcomes for women with diabetes who maintain excellent glucose control during their pregnancy are very good, and are similar to those seen in the general population, according to the results of a retrospective study.

The study, conducted by the high-risk obstetrics/endocrinology clinic at the Nebraska Medical Center, Omaha, found a low rate of diabetes-related obstetric complications in a group of 100 women who attended the clinic during their pregnancies.

The clinic has used a team approach, incorporating intensive insulin and specific targets, since 1997. That approach “can result in excellent glucose control in at least half of patients, with overall maternal and fetal outcomes similar to” those in the general population, Dr. Kara Meinke Baehr said in a poster presented at the annual meeting of the Endocrine Society.

The team includes perinatologists, endocrinologists, certified diabetes educators, registered dietitians, a social worker, and a translator.

Dr. Meinke Baehr of the Nebraska Medical Center and her colleagues reviewed the records of 100 women whose pregnancies were managed at the clinic from 1997 to 2006. Fetal outcomes were compared with the Nebraska 2004 Vital Statistics report.

The mean age at enrollment in the clinic was 29 years; the mean prepregnancy body mass index was 32 kg/m

More than a third of the women (36%) had type 1 diabetes; 26% had type 2 diabetes; 26% had gestational diabetes that was managed with insulin; and 12% had gestational diabetes that was managed by diet.

Women with types 1 and 2 diabetes significantly improved their blood glucose levels during the second and third trimesters of their pregnancies. At 8 weeks, only 25% had a hemoglobin A1c (HbA1c) value of less than 7%. That number rose to 80% by week 16 and to 90% by week 24; it then dropped back to 80% by week 32.

By the second half of pregnancy, about half of the cohort was meeting the goal of an HbA1c value of 6% or less, a significant improvement from the first trimester .

Maternal complications during pregnancy included retinopathy (6%), proteinuria (38%), and pre-eclampsia (17%). There were 104 hospitalizations, more than half of which were for glucose control. One of the women was admitted 10 times.

Insulin regimens were used in 115 of the 127 pregnancies (90%). At the time of delivery, 43% were taking four injections per day; 2% were taking one insulin injection per day; 22% were taking two injections per day; and 3% were taking three injections per day. In all, 20% of the women were using an insulin pump.

There were 127 pregnancies among these women over the study period, including 121 live births with two sets of twins. Most of the deliveries (71%) were by cesarean section; the rest were vaginal.

The mean gestational age was 37 weeks. Apgar scores were good, with a mean of 7.4 at 1 minute and 8.5 at 5 minutes. The mean birth weight was 3,479 grams; 28% of the infants were macrosomic. Overall, 35% of the infants required a stay in the neonatal intensive care unit (mean length of stay, 16 days).

The rate of birth trauma was 2%; traumas included Erb's palsy and shoulder dystocia. The rate of birth defects was 7%. Such defects included one schizencephaly, one tracheoesophageal fistula, one transposition of the great vessels, one polydactyly, and two cases of patent ductus arteriosus.

All of the rates were lower than those in the 2004 Nebraska state report, but comparisons can't be drawn because of the small study sample, Dr. Meinke Baehr noted.

SAN FRANCISCO — Pregnancy outcomes for women with diabetes who maintain excellent glucose control during their pregnancy are very good, and are similar to those seen in the general population, according to the results of a retrospective study.

The study, conducted by the high-risk obstetrics/endocrinology clinic at the Nebraska Medical Center, Omaha, found a low rate of diabetes-related obstetric complications in a group of 100 women who attended the clinic during their pregnancies.

The clinic has used a team approach, incorporating intensive insulin and specific targets, since 1997. That approach “can result in excellent glucose control in at least half of patients, with overall maternal and fetal outcomes similar to” those in the general population, Dr. Kara Meinke Baehr said in a poster presented at the annual meeting of the Endocrine Society.

The team includes perinatologists, endocrinologists, certified diabetes educators, registered dietitians, a social worker, and a translator.

Dr. Meinke Baehr of the Nebraska Medical Center and her colleagues reviewed the records of 100 women whose pregnancies were managed at the clinic from 1997 to 2006. Fetal outcomes were compared with the Nebraska 2004 Vital Statistics report.

The mean age at enrollment in the clinic was 29 years; the mean prepregnancy body mass index was 32 kg/m

More than a third of the women (36%) had type 1 diabetes; 26% had type 2 diabetes; 26% had gestational diabetes that was managed with insulin; and 12% had gestational diabetes that was managed by diet.

Women with types 1 and 2 diabetes significantly improved their blood glucose levels during the second and third trimesters of their pregnancies. At 8 weeks, only 25% had a hemoglobin A1c (HbA1c) value of less than 7%. That number rose to 80% by week 16 and to 90% by week 24; it then dropped back to 80% by week 32.

By the second half of pregnancy, about half of the cohort was meeting the goal of an HbA1c value of 6% or less, a significant improvement from the first trimester .

Maternal complications during pregnancy included retinopathy (6%), proteinuria (38%), and pre-eclampsia (17%). There were 104 hospitalizations, more than half of which were for glucose control. One of the women was admitted 10 times.

Insulin regimens were used in 115 of the 127 pregnancies (90%). At the time of delivery, 43% were taking four injections per day; 2% were taking one insulin injection per day; 22% were taking two injections per day; and 3% were taking three injections per day. In all, 20% of the women were using an insulin pump.

There were 127 pregnancies among these women over the study period, including 121 live births with two sets of twins. Most of the deliveries (71%) were by cesarean section; the rest were vaginal.

The mean gestational age was 37 weeks. Apgar scores were good, with a mean of 7.4 at 1 minute and 8.5 at 5 minutes. The mean birth weight was 3,479 grams; 28% of the infants were macrosomic. Overall, 35% of the infants required a stay in the neonatal intensive care unit (mean length of stay, 16 days).

The rate of birth trauma was 2%; traumas included Erb's palsy and shoulder dystocia. The rate of birth defects was 7%. Such defects included one schizencephaly, one tracheoesophageal fistula, one transposition of the great vessels, one polydactyly, and two cases of patent ductus arteriosus.

All of the rates were lower than those in the 2004 Nebraska state report, but comparisons can't be drawn because of the small study sample, Dr. Meinke Baehr noted.

SAN FRANCISCO – Metformin appears to exert its weight-loss effects in obese children by reducing their desire to eat and thus decreasing their food intake.

A substudy of a government-sponsored placebo-controlled trial found that children taking metformin not only ate less, they reported higher satiety and lower hunger than those taking placebo, Rachael Sorg said in a poster session at the annual meeting of the Endocrine Society.

The 6-month study, sponsored by the National Institutes of Health, randomized 100 obese children with severe hyperinsulinemia (mean age 10 years) to either 1,000 mg metformin twice a day or to placebo. Some of the children (45 metformin-treated and 39 placebo-treated) participated in pre- and posttreatment meal studies to evaluate the drug's effect on food intake. One study was conducted before the drug trial commenced and one at the end of the 6-month treatment period.

Each meal study included two buffet lunches, each containing 28 items (9,835 calories total). The first lunch was consumed after children fasted through the night. The second was consumed after they drank a 790-calorie nutrient shake for breakfast.

Subjects completed a scale of hunger, fullness, and desire to eat before after each test meal, and also kept a food diary of everything they consumed for 7 days before and after the test.

Compared with baseline measurements obtained in the pre-metformin meal study, children taking metformin consumed significantly fewer calories in the meal after the breakfast shake and reported significantly decreased feelings of hunger and increased feelings of fullness. They reported lower hunger after the postshake meal, lower desire to eat the postshake meal, and lower caloric intake at the postfast meal as well, although none of these differences were significant.

“These data suggest that one of the mechanisms whereby metformin treatment reduces body weight in overweight, hyperinsulinemic children is by decreasing food intake and perceived hunger,” said Ms. Sorg, a research assistant at the National Institutes of Child Health and Human Development.

SAN FRANCISCO – Metformin appears to exert its weight-loss effects in obese children by reducing their desire to eat and thus decreasing their food intake.

A substudy of a government-sponsored placebo-controlled trial found that children taking metformin not only ate less, they reported higher satiety and lower hunger than those taking placebo, Rachael Sorg said in a poster session at the annual meeting of the Endocrine Society.

The 6-month study, sponsored by the National Institutes of Health, randomized 100 obese children with severe hyperinsulinemia (mean age 10 years) to either 1,000 mg metformin twice a day or to placebo. Some of the children (45 metformin-treated and 39 placebo-treated) participated in pre- and posttreatment meal studies to evaluate the drug's effect on food intake. One study was conducted before the drug trial commenced and one at the end of the 6-month treatment period.

Each meal study included two buffet lunches, each containing 28 items (9,835 calories total). The first lunch was consumed after children fasted through the night. The second was consumed after they drank a 790-calorie nutrient shake for breakfast.

Subjects completed a scale of hunger, fullness, and desire to eat before after each test meal, and also kept a food diary of everything they consumed for 7 days before and after the test.

Compared with baseline measurements obtained in the pre-metformin meal study, children taking metformin consumed significantly fewer calories in the meal after the breakfast shake and reported significantly decreased feelings of hunger and increased feelings of fullness. They reported lower hunger after the postshake meal, lower desire to eat the postshake meal, and lower caloric intake at the postfast meal as well, although none of these differences were significant.

“These data suggest that one of the mechanisms whereby metformin treatment reduces body weight in overweight, hyperinsulinemic children is by decreasing food intake and perceived hunger,” said Ms. Sorg, a research assistant at the National Institutes of Child Health and Human Development.

SAN FRANCISCO – Metformin appears to exert its weight-loss effects in obese children by reducing their desire to eat and thus decreasing their food intake.

A substudy of a government-sponsored placebo-controlled trial found that children taking metformin not only ate less, they reported higher satiety and lower hunger than those taking placebo, Rachael Sorg said in a poster session at the annual meeting of the Endocrine Society.

The 6-month study, sponsored by the National Institutes of Health, randomized 100 obese children with severe hyperinsulinemia (mean age 10 years) to either 1,000 mg metformin twice a day or to placebo. Some of the children (45 metformin-treated and 39 placebo-treated) participated in pre- and posttreatment meal studies to evaluate the drug's effect on food intake. One study was conducted before the drug trial commenced and one at the end of the 6-month treatment period.

Each meal study included two buffet lunches, each containing 28 items (9,835 calories total). The first lunch was consumed after children fasted through the night. The second was consumed after they drank a 790-calorie nutrient shake for breakfast.

Subjects completed a scale of hunger, fullness, and desire to eat before after each test meal, and also kept a food diary of everything they consumed for 7 days before and after the test.

Compared with baseline measurements obtained in the pre-metformin meal study, children taking metformin consumed significantly fewer calories in the meal after the breakfast shake and reported significantly decreased feelings of hunger and increased feelings of fullness. They reported lower hunger after the postshake meal, lower desire to eat the postshake meal, and lower caloric intake at the postfast meal as well, although none of these differences were significant.

“These data suggest that one of the mechanisms whereby metformin treatment reduces body weight in overweight, hyperinsulinemic children is by decreasing food intake and perceived hunger,” said Ms. Sorg, a research assistant at the National Institutes of Child Health and Human Development.

WILLIAMSBURG, VA. — Imiquimod can be a powerful tool for fighting in situ squamous cell carcinomas and superficial basal cell carcinomas, Dr. Roger Ceilley said.

"A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas," said Dr. Ceilley, at the annual meeting of the American Society for Mohs Surgery. "We may worry that when treating carcinoma in situ topically, that we are just treating the tip of the iceberg, but there are a few studies now that show even patients with an early invasive squamous cell carcinoma [SCC] treated three times a week for 12 weeks show clearing of the deeper component of the lesion."

Evidence is mounting for imiquimod's use on various sites of SCC in situ, including lesions on the anterior leg and penis, said Dr. Ceilley, a professor of dermatology at the University of Iowa, Iowa City. He noted seven case reports of imiquimod used successfully to treat penile lesions. The cream was applied anywhere from twice a week to every other day, depending on individual tolerance, for 8-16 weeks. "This is clearly an off-label use and you wouldn't want to do it without consulting a urologist but, with close management, this might be an alternative for an SCC that would otherwise result in a penectomy," he said.

Combined with 5-fluorouracil, imiquimod is especially effective for SCC lesions on the scalp, and dorsum of the hand—places that are often resistant to either treatment alone.

The cream also is approved for use in superficial basal cell carcinoma, where it has shown effectiveness. A 2004 placebo-controlled study found that up to 82% of patients had histologic clearance after a 6-week treatment cycle (J. Am. Acad. Dermatol. 2004;50:722-33). The study also found no significant difference in clearance rates among patients who used the cream five or seven times a week, lending support for the shorter treatment time. However, clearance was highly correlated with increased severity of erythema, erosion, and scabbing or crusting. The cosmetic outcomes were excellent.

For BCC, Dr. Ceilley said he prefers to use imiquimod prior to Mohs surgery, in conjunction with aggressive curettage and electrodesiccation. Treating for a few weeks preoperatively can reduce the defect, decrease the frequency of residual tumor, and improve cosmetic appearance.

"You can really define the lesions more carefully, minimizing the area of surgery you have to do," he said.

Evidence is mounting for the use of imiquimod in nodular BCC as well—especially in smaller, low-risk lesions or as adjunctive therapy. The original 2002 dosing study found a histologic clearance rate of up to 76%, with no significant difference between those who applied the medication daily for 12 or 16 weeks (Arch. Dermatol. 2002;138:1165-71), said Dr. Ceilley.

A more recent study found that while 70 of 90 patients (78%) had a complete clinical response, there was clinically visible tumor still present in 20 patients (22%). There was complete histopathologic clearance observed in 58 patients (64%), while residual tumor remained in 32 patients (36%). Efficacy was better in lesions smaller than 1 cm in diameter. The authors concluded that, since 17% of patients in the study with clinical clearance still had pathologic evidence of disease, excisional biopsy of the treated site is still indicated (J. Am. Acad. Dermatol. 2007;57:616-21).

Dr. Ceilley stated that he did not have any conflicts of interest to disclose.

'A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas.' DR. CEILLEY

WILLIAMSBURG, VA. — Imiquimod can be a powerful tool for fighting in situ squamous cell carcinomas and superficial basal cell carcinomas, Dr. Roger Ceilley said.

"A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas," said Dr. Ceilley, at the annual meeting of the American Society for Mohs Surgery. "We may worry that when treating carcinoma in situ topically, that we are just treating the tip of the iceberg, but there are a few studies now that show even patients with an early invasive squamous cell carcinoma [SCC] treated three times a week for 12 weeks show clearing of the deeper component of the lesion."

Evidence is mounting for imiquimod's use on various sites of SCC in situ, including lesions on the anterior leg and penis, said Dr. Ceilley, a professor of dermatology at the University of Iowa, Iowa City. He noted seven case reports of imiquimod used successfully to treat penile lesions. The cream was applied anywhere from twice a week to every other day, depending on individual tolerance, for 8-16 weeks. "This is clearly an off-label use and you wouldn't want to do it without consulting a urologist but, with close management, this might be an alternative for an SCC that would otherwise result in a penectomy," he said.

Combined with 5-fluorouracil, imiquimod is especially effective for SCC lesions on the scalp, and dorsum of the hand—places that are often resistant to either treatment alone.

The cream also is approved for use in superficial basal cell carcinoma, where it has shown effectiveness. A 2004 placebo-controlled study found that up to 82% of patients had histologic clearance after a 6-week treatment cycle (J. Am. Acad. Dermatol. 2004;50:722-33). The study also found no significant difference in clearance rates among patients who used the cream five or seven times a week, lending support for the shorter treatment time. However, clearance was highly correlated with increased severity of erythema, erosion, and scabbing or crusting. The cosmetic outcomes were excellent.

For BCC, Dr. Ceilley said he prefers to use imiquimod prior to Mohs surgery, in conjunction with aggressive curettage and electrodesiccation. Treating for a few weeks preoperatively can reduce the defect, decrease the frequency of residual tumor, and improve cosmetic appearance.

"You can really define the lesions more carefully, minimizing the area of surgery you have to do," he said.

Evidence is mounting for the use of imiquimod in nodular BCC as well—especially in smaller, low-risk lesions or as adjunctive therapy. The original 2002 dosing study found a histologic clearance rate of up to 76%, with no significant difference between those who applied the medication daily for 12 or 16 weeks (Arch. Dermatol. 2002;138:1165-71), said Dr. Ceilley.

A more recent study found that while 70 of 90 patients (78%) had a complete clinical response, there was clinically visible tumor still present in 20 patients (22%). There was complete histopathologic clearance observed in 58 patients (64%), while residual tumor remained in 32 patients (36%). Efficacy was better in lesions smaller than 1 cm in diameter. The authors concluded that, since 17% of patients in the study with clinical clearance still had pathologic evidence of disease, excisional biopsy of the treated site is still indicated (J. Am. Acad. Dermatol. 2007;57:616-21).

Dr. Ceilley stated that he did not have any conflicts of interest to disclose.

'A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas.' DR. CEILLEY

WILLIAMSBURG, VA. — Imiquimod can be a powerful tool for fighting in situ squamous cell carcinomas and superficial basal cell carcinomas, Dr. Roger Ceilley said.

"A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas," said Dr. Ceilley, at the annual meeting of the American Society for Mohs Surgery. "We may worry that when treating carcinoma in situ topically, that we are just treating the tip of the iceberg, but there are a few studies now that show even patients with an early invasive squamous cell carcinoma [SCC] treated three times a week for 12 weeks show clearing of the deeper component of the lesion."

Evidence is mounting for imiquimod's use on various sites of SCC in situ, including lesions on the anterior leg and penis, said Dr. Ceilley, a professor of dermatology at the University of Iowa, Iowa City. He noted seven case reports of imiquimod used successfully to treat penile lesions. The cream was applied anywhere from twice a week to every other day, depending on individual tolerance, for 8-16 weeks. "This is clearly an off-label use and you wouldn't want to do it without consulting a urologist but, with close management, this might be an alternative for an SCC that would otherwise result in a penectomy," he said.

Combined with 5-fluorouracil, imiquimod is especially effective for SCC lesions on the scalp, and dorsum of the hand—places that are often resistant to either treatment alone.

The cream also is approved for use in superficial basal cell carcinoma, where it has shown effectiveness. A 2004 placebo-controlled study found that up to 82% of patients had histologic clearance after a 6-week treatment cycle (J. Am. Acad. Dermatol. 2004;50:722-33). The study also found no significant difference in clearance rates among patients who used the cream five or seven times a week, lending support for the shorter treatment time. However, clearance was highly correlated with increased severity of erythema, erosion, and scabbing or crusting. The cosmetic outcomes were excellent.

For BCC, Dr. Ceilley said he prefers to use imiquimod prior to Mohs surgery, in conjunction with aggressive curettage and electrodesiccation. Treating for a few weeks preoperatively can reduce the defect, decrease the frequency of residual tumor, and improve cosmetic appearance.

"You can really define the lesions more carefully, minimizing the area of surgery you have to do," he said.

Evidence is mounting for the use of imiquimod in nodular BCC as well—especially in smaller, low-risk lesions or as adjunctive therapy. The original 2002 dosing study found a histologic clearance rate of up to 76%, with no significant difference between those who applied the medication daily for 12 or 16 weeks (Arch. Dermatol. 2002;138:1165-71), said Dr. Ceilley.

A more recent study found that while 70 of 90 patients (78%) had a complete clinical response, there was clinically visible tumor still present in 20 patients (22%). There was complete histopathologic clearance observed in 58 patients (64%), while residual tumor remained in 32 patients (36%). Efficacy was better in lesions smaller than 1 cm in diameter. The authors concluded that, since 17% of patients in the study with clinical clearance still had pathologic evidence of disease, excisional biopsy of the treated site is still indicated (J. Am. Acad. Dermatol. 2007;57:616-21).

Dr. Ceilley stated that he did not have any conflicts of interest to disclose.

'A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas.' DR. CEILLEY

SAN FRANCISCO — Even moderate physical fitness appears to confer a significant survival benefit on men with type 2 diabetes, no matter what their body weight, according to Roshney Jacob-Issac, Ph.D.

Her retrospective study, presented at the annual meeting of the Endocrine Society, found an inverse association between mortality and increasing fitness, with normal- and overweight men gaining even more survival benefits as they reached the highest fitness levels. Although obese men did not reap any extra survival benefit with the top fitness level, moderate fitness decreased their overall risk of death by 52%.

“Increasing physical fitness has a survival benefit in diabetes regardless of body mass index,” said Dr. Jacob-Issac of the Veterans Affairs Medical Center, in Washington. “For this reason, we suggest that moderate physical activity be advocated for all patients with diabetes.”

Her retrospective study examined the link between all-cause mortality and exercise capacity in 2,690 men with type 2 diabetes, all of whom were referred for exercise tolerance testing at VA centers in Washington, D.C., or Palo Alto, Calif. Nearly half of the men (1,196) were obese; 1,088 were overweight, and 406 had a normal BMI.

The study did not include any men who, during testing, had a positive stress test, unstable symptoms, or a left bundle branch block; it also excluded anyone with an implanted pacemaker or impaired chronotropic response.

Peak work load, which was determined via a stress test, was estimated in metabolic equivalents (METs). One MET is the energy expenditure at rest, or an oxygen consumption of 3.5 mL/kg a minute. Based on peak workload, individuals were categorized as low fit (5 or fewer METs), moderately fit (5.1–8 METs), or highly fit (more than 8 METs). All-cause mortality was assessed at a mean of 7 years.

There were 762 deaths (172 in the normal-weight group, 334 in the overweight group, and 256 in the obese group). After adjusting for age, cardiac medications, and cardiovascular disease risk factors, Dr. Jacob-Issac found a strong, graded relationship between increasing fitness and decreasing mortality in all three groups.

In normal weight men, moderate fitness conferred a 40% reduction in the risk of death and high fitness conferred a 60% risk reduction, compared with low fitness. In overweight men, the risk reduction was 40% for moderate fitness and 65% for high fitness, compared with low fitness.

In obese men, moderate fitness conferred a 52% reduction in the risk of death, but being highly fit conferred no additional protection. This might be because of the very small number of men who were both obese and highly fit, Dr. Jacob-Issac noted.

A separate analysis concluded fitness level was a better predictor of mortality than age, BMI, hypertension, or dyslipidemia.

Dr. Jacob-Issac reported no conflict of interest related to the study.

SAN FRANCISCO — Even moderate physical fitness appears to confer a significant survival benefit on men with type 2 diabetes, no matter what their body weight, according to Roshney Jacob-Issac, Ph.D.

Her retrospective study, presented at the annual meeting of the Endocrine Society, found an inverse association between mortality and increasing fitness, with normal- and overweight men gaining even more survival benefits as they reached the highest fitness levels. Although obese men did not reap any extra survival benefit with the top fitness level, moderate fitness decreased their overall risk of death by 52%.

“Increasing physical fitness has a survival benefit in diabetes regardless of body mass index,” said Dr. Jacob-Issac of the Veterans Affairs Medical Center, in Washington. “For this reason, we suggest that moderate physical activity be advocated for all patients with diabetes.”

Her retrospective study examined the link between all-cause mortality and exercise capacity in 2,690 men with type 2 diabetes, all of whom were referred for exercise tolerance testing at VA centers in Washington, D.C., or Palo Alto, Calif. Nearly half of the men (1,196) were obese; 1,088 were overweight, and 406 had a normal BMI.

The study did not include any men who, during testing, had a positive stress test, unstable symptoms, or a left bundle branch block; it also excluded anyone with an implanted pacemaker or impaired chronotropic response.

Peak work load, which was determined via a stress test, was estimated in metabolic equivalents (METs). One MET is the energy expenditure at rest, or an oxygen consumption of 3.5 mL/kg a minute. Based on peak workload, individuals were categorized as low fit (5 or fewer METs), moderately fit (5.1–8 METs), or highly fit (more than 8 METs). All-cause mortality was assessed at a mean of 7 years.

There were 762 deaths (172 in the normal-weight group, 334 in the overweight group, and 256 in the obese group). After adjusting for age, cardiac medications, and cardiovascular disease risk factors, Dr. Jacob-Issac found a strong, graded relationship between increasing fitness and decreasing mortality in all three groups.

In normal weight men, moderate fitness conferred a 40% reduction in the risk of death and high fitness conferred a 60% risk reduction, compared with low fitness. In overweight men, the risk reduction was 40% for moderate fitness and 65% for high fitness, compared with low fitness.

In obese men, moderate fitness conferred a 52% reduction in the risk of death, but being highly fit conferred no additional protection. This might be because of the very small number of men who were both obese and highly fit, Dr. Jacob-Issac noted.

A separate analysis concluded fitness level was a better predictor of mortality than age, BMI, hypertension, or dyslipidemia.

Dr. Jacob-Issac reported no conflict of interest related to the study.

SAN FRANCISCO — Even moderate physical fitness appears to confer a significant survival benefit on men with type 2 diabetes, no matter what their body weight, according to Roshney Jacob-Issac, Ph.D.

Her retrospective study, presented at the annual meeting of the Endocrine Society, found an inverse association between mortality and increasing fitness, with normal- and overweight men gaining even more survival benefits as they reached the highest fitness levels. Although obese men did not reap any extra survival benefit with the top fitness level, moderate fitness decreased their overall risk of death by 52%.

“Increasing physical fitness has a survival benefit in diabetes regardless of body mass index,” said Dr. Jacob-Issac of the Veterans Affairs Medical Center, in Washington. “For this reason, we suggest that moderate physical activity be advocated for all patients with diabetes.”

Her retrospective study examined the link between all-cause mortality and exercise capacity in 2,690 men with type 2 diabetes, all of whom were referred for exercise tolerance testing at VA centers in Washington, D.C., or Palo Alto, Calif. Nearly half of the men (1,196) were obese; 1,088 were overweight, and 406 had a normal BMI.

The study did not include any men who, during testing, had a positive stress test, unstable symptoms, or a left bundle branch block; it also excluded anyone with an implanted pacemaker or impaired chronotropic response.

Peak work load, which was determined via a stress test, was estimated in metabolic equivalents (METs). One MET is the energy expenditure at rest, or an oxygen consumption of 3.5 mL/kg a minute. Based on peak workload, individuals were categorized as low fit (5 or fewer METs), moderately fit (5.1–8 METs), or highly fit (more than 8 METs). All-cause mortality was assessed at a mean of 7 years.

There were 762 deaths (172 in the normal-weight group, 334 in the overweight group, and 256 in the obese group). After adjusting for age, cardiac medications, and cardiovascular disease risk factors, Dr. Jacob-Issac found a strong, graded relationship between increasing fitness and decreasing mortality in all three groups.

In normal weight men, moderate fitness conferred a 40% reduction in the risk of death and high fitness conferred a 60% risk reduction, compared with low fitness. In overweight men, the risk reduction was 40% for moderate fitness and 65% for high fitness, compared with low fitness.

In obese men, moderate fitness conferred a 52% reduction in the risk of death, but being highly fit conferred no additional protection. This might be because of the very small number of men who were both obese and highly fit, Dr. Jacob-Issac noted.

A separate analysis concluded fitness level was a better predictor of mortality than age, BMI, hypertension, or dyslipidemia.

Dr. Jacob-Issac reported no conflict of interest related to the study.